Division of Early Drug Development, European Institute of Oncology, IRCCS, 20141 Milan, Italy; Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, 20122, Italy.
Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, 20122, Italy; Division of Cancer Prevention and Genetics, European Institute of Oncology (IEO) IRCCS, 20141 Milan, Italy.
Eur J Cancer. 2023 Apr;183:79-89. doi: 10.1016/j.ejca.2023.01.019. Epub 2023 Jan 31.
Precision oncology aims to improve clinical outcomes by personalising treatment options for patients with cancer. Exploiting vulnerabilities identified in a patient's cancer genome requires reliable interpretation of a huge mole of alterations and heterogeneous biomarkers. ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) allows evidence-based evaluation of genomic findings. Molecular tumour boards (MTBs) convey the required multi-disciplinary expertise to enable ESCAT evaluation and strategical treatment choice.
We retrospectively reviewed the records of 251 consecutive patients discussed by European Institute of Oncology MTB between June 2019 and June 2022.
One-hundred eighty-eight (74.6%) patients had at least one actionable alteration. After MTB discussion, 76 patients received molecularly matched therapies (MMTs) while 76 patients received standard of care. Patients receiving MMT displayed higher overall response rate (37.3% versus 12.9%), median progression-free survival (mPFS 5.8 months, 95% confidence interval [CI] 4.1-7.5 versus 3.6 months, 95% CI 2.5-4.8, p = 0.041; hazard ratio 0.679, 95% CI 0.467-0.987) and median overall survival (mOS 35.1 months, 95% CI not evaluable versus 8.5 months, 95% CI 3.8-13.2; hazard ratio 0.431, 95% CI 0.250-0.744, p = 0.002). Superiority in OS and PFS persisted in multivariable models. Among 61 pretreated patients receiving MMT, 37.5% of patients had PFS2/PFS1 ratio ≥1.3. Patients with higher actionable targets (ESCAT tier I) had better OS (p = 0.001) and PFS (p = 0.049), while no difference was observed in lower evidence levels.
Our experience shows that MTBs can yield valuable clinical benefit. Higher actionability ESCAT level appears to be associated with better outcomes for patients receiving MMT.
精准肿瘤学旨在通过为癌症患者制定个性化治疗方案来提高临床疗效。利用患者癌症基因组中发现的弱点需要可靠地解释大量的改变和异质生物标志物。欧洲肿瘤内科学会(ESMO)分子靶向治疗临床可操作性量表(ESCAT)允许对基因组发现进行基于证据的评估。分子肿瘤委员会(MTB)提供所需的多学科专业知识,以进行 ESCAT 评估和策略性治疗选择。
我们回顾性分析了 2019 年 6 月至 2022 年 6 月期间欧洲肿瘤研究所 MTB 讨论的 251 例连续患者的记录。
188 例(74.6%)患者至少存在一个可操作的改变。在 MTB 讨论后,76 例患者接受了分子匹配治疗(MMTs),而 76 例患者接受了标准治疗。接受 MMT 的患者显示出更高的总体缓解率(37.3%比 12.9%)、中位无进展生存期(mPFS 5.8 个月,95%CI 4.1-7.5 比 3.6 个月,95%CI 2.5-4.8,p=0.041;风险比 0.679,95%CI 0.467-0.987)和中位总生存期(mOS 35.1 个月,95%CI 不可评估比 8.5 个月,95%CI 3.8-13.2;风险比 0.431,95%CI 0.250-0.744,p=0.002)。在多变量模型中,OS 和 PFS 的优势仍然存在。在 61 例接受 MMT 的预处理患者中,37.5%的患者 PFS2/PFS1 比值≥1.3。具有更高可操作性靶点(ESCAT Ⅰ级)的患者具有更好的 OS(p=0.001)和 PFS(p=0.049),而较低证据水平的患者则没有差异。
我们的经验表明,MTB 可以带来有价值的临床获益。更高的 ESCAT 可操作性水平似乎与接受 MMT 的患者的更好结局相关。